ArticleClinical and translational medicine2025
Identification of CENPM as a key gene driving adrenocortical carcinoma metastasis via physical interaction with immune checkpoint ligand FGL1.
Article in Clinical and translational medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed.
- Targeting centromere protein M represses cell growth and mobility via inactivating AKT pathway but less affects BRAF inhibitor sensitivity in cutaneous melanoma.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- CENPM as a biomarker and therapeutic target for lymph node metastasis in thyroid carcinoma.Frontiers in genetics · 2026Article
- Unraveling fibrinogen-like protein 1's role in immune regulation.Frontiers in immunology · 2026Review
- Defactinib in Combination with Mitotane Can Be an Effective Treatment in Human Adrenocortical Carcinoma.International journal of molecular sciences · 2025Article
- Identification of Cancer Associated Fibroblasts Related Genes Signature to Facilitate Improved Prediction of Prognosis and Responses to Therapy in Patients with Pancreatic Cancer.International journal of molecular sciences · 2025Article
- Identification of CENPM as a key gene driving adrenocortical carcinoma metastasis via physical interaction with immune checkpoint ligand FGL1.Clinical and translational medicine · 2025Article
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11 authors.
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Abstract
backgroundDistant metastasis occurs in the majority of adrenocortical carcinoma (ACC), leading to an extremely poor prognosis. However, the key genes driving ACC metastasis remain unclear.
methodsWeighted gene co-expression network analysis (WGCNA) and functional enrichment analysis were conducted to identify ACC metastasis-related genes. Data from RNA-seq and microarray were analyzed to reveal correlations of the CENPM gene with cancer, metastasis, and survival in ACC. Immunohistochemistry was used to assess CENPM protein expression. The impact of CENPM on metastasis behaviour was verified in ACC (H295R and SW-13) cells and xenograft NPG mice. DIA quantitative proteomics analysis, western blot, immunofluorescence, and co-immunoprecipitation assay were performed to identify the downstream target of CENPM.
resultsAmong the 12 035 analyzed genes, 363 genes were related to ACC metastasis and CENPM was identified as the hub gene. CENPM was upregulated in ACC samples and associated with metastasis and poor prognosis. Knockdown of CENPM inhibited proliferation, invasion, and migration of ACC cells and suppressed liver metastasis in xenograft NPG mice. Collagen-containing extracellular matrix signalling was primarily downregulated when CENPM was knocked down. FGL1, important components of ECM signalling and immune checkpoint ligand of LAG3, were downregulated following CENPM silence, overexpressed in human advanced ACC samples, and colocalized with CENPM. Physical interaction between CENPM and FGL1 was identified. Overexpression of FGL1 rescued migration and invasion of CENPM knockdown ACC cells.
conclusionsCENPM is a key gene in driving ACC metastasis. CENPM promotes ACC metastasis through physical interaction with the immune checkpoint ligand FGL1. CENPM can be used as a new prognostic biomarker and therapeutic target for metastatic ACC. HIGHLIGHTS: CENPM is the key gene that drives ACC metastasis, and a robust biomarker for ACC prognosis. Silencing CENPM impedes ACC metastasis in vitro and in vivo by physical interaction with immune checkpoint ligand FGL1. FGL1 is overexpressed in ACC and promotes ACC metastasis.
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